Ivanov Andrei I, Korolenko Elena A, Korolik Elena V, Firsov Stanislav P, Zhbankov Rostislav G, Marchewka Mariusz K, Ratajczak Henryk
Department of Pathology and Laboratory Medicine, Emory University, Whitehead Medical Building, Room 123, 615 Michael Street, Atlanta, GA 30322, USA.
Arch Biochem Biophys. 2002 Dec 1;408(1):69-77. doi: 10.1016/s0003-9861(02)00533-7.
Human serum albumin (HSA) binding with endogenous metabolites and drugs is substantially decreased in chronic renal and liver diseases. To test the hypothesis that the decreased binding ability is caused by conformational changes of the protein, we analyzed infrared and Raman spectra of HSA isolated from healthy donors and patients with chronic uremia and liver cirrhosis. Uremia did not affect the secondary structure of HSA but modified the environment of its Asp/Glu residues. Liver cirrhosis increased the amount of extended and beta-structures, modified the environment of Asp/Glu and Tyr side chains, and changed the configuration of disulfide bridges in albumin molecules. The conformational changes of "cirrhotic" albumin were not caused by reversibly bound ligands and resembled a partial unfolding of the protein induced by adsorption on the charcoal surface. The dramatic structural alterations of HSA in liver cirrhosis may be caused by its oxidative modification and might underlie the decreased binding ability and changed body distribution of albumin.
在慢性肾脏疾病和肝脏疾病中，人血清白蛋白（HSA）与内源性代谢物和药物的结合能力显著下降。为了验证结合能力下降是由蛋白质构象变化引起的这一假设，我们分析了从健康供体以及患有慢性尿毒症和肝硬化的患者中分离出的HSA的红外光谱和拉曼光谱。尿毒症并未影响HSA的二级结构，但改变了其天冬氨酸/谷氨酸残基的环境。肝硬化增加了伸展结构和β结构的数量，改变了天冬氨酸/谷氨酸和酪氨酸侧链的环境，并改变了白蛋白分子中二硫键的构型。“肝硬化型”白蛋白的构象变化并非由可逆结合的配体引起，而是类似于蛋白质吸附在木炭表面所诱导的部分解折叠。肝硬化中HSA的显著结构改变可能是由其氧化修饰引起的，这可能是白蛋白结合能力下降和体内分布改变的基础。
